A worldwide quest is under way to find new treatments to stop, slow or even prevent Alzheimer's. Because new drugs take years to produce from concept to market—and because drugs that seem promising in early-stage studies may not work as hoped in large-scale trials—it is critical that Alzheimer's and related dementias research continue to accelerate. To ensure that the effort to find better treatments receives the focus it deserves, the Alzheimer's Association funds researchers looking at new treatment strategies and advocates for more federal funding of Alzheimer's research.

The hope for future drugs

Currently, there are five FDA-approved Alzheimer's drugs that treat the symptoms of Alzheimer's — temporarily helping memory and thinking problems in about half of the people who take them. But these medications do not treat the underlying causes of Alzheimer's.

In contrast, many of the new drugs in development aim to modify the disease process itself, by impacting one or more of the many wide-ranging brain changes that Alzheimer's causes. These changes offer potential "targets" for new drugs to stop or slow the progress of the disease. Many researchers believe successful treatment will eventually involve a "cocktail" of medications aimed at several targets, similar to current state-of-the-art treatments for many cancers and AIDS. Sign up for our weekly e-news and stay up-to-date on the latest advances in Alzheimer's treatments, care and research.

"Despite increasing momentum in Alzheimer's research, we still have two main obstacles to overcome. First, we need volunteers for clinical trials. Volunteering to participate in a study is one of the greatest ways someone can help move Alzheimer's research forward. Second, we need a significant increase in federal research funding. Investing in research now will cost our nation far less than the cost of care for the rising number of Americans who will be affected by Alzheimer's in coming decades."- Bill Thies, Ph.D., Senior Scientist in Residence, Alzheimer’s Association

Targets for future drugs

Over the last 30 years, researchers have made remarkable progress in understanding healthy brain function and what goes wrong in Alzheimer's disease. The following are examples of promising targets for next-generation drug therapies under investigation in current research studies:

Beta-amyloid is the chief component of plaques, one hallmark Alzheimer's brain abnormality. Scientists now have a detailed understanding of how this protein fragment is clipped from its parent compound amyloid precursor protein (APP) by two enzymes — beta-secretase and gamma-secretase. Researchers are developing medications aimed at virtually every point in amyloid processing. This includes blocking activity of both enzymes; preventing the beta-amyloid fragments from clumping into plaques; and even using antibodies against beta-amyloid to clear it from the brain. Several clinical trials of investigational drugs targeting beta-amyloid are included below in the key clinical trial summaries.

Tau protein is the chief component of tangles, the other hallmark brain abnormality. Researchers are investigating strategies to keep tau molecules from collapsing and twisting into tangles, a process that destroys a vital cell transport system.

Inflammation is another key Alzheimer's brain abnormality. Scientists have learned a great deal about molecules involved in the body's overall inflammatory response and are working to better understand specific aspects of inflammation most active in the brain. These insights may point to novel anti-inflammatory treatments for Alzheimer's disease.

Insulin resistance and the way brain cells process insulin may be linked to Alzheimer's disease. Researchers are exploring the role of insulin in the brain and closely related questions of how brain cells use sugar and produce energy. These investigations may reveal strategies to support cell function and stave off Alzheimer-related changes.

Gauging treatment impact with brain imaging and biomarkers
In addition to investigating experimental drugs, many clinical trials in progress include various brain imaging studies and testing of blood or spinal fluid. Researchers hope these techniques will one day provide methods to diagnose Alzheimer's disease in its earliest, most treatable stages — possibly even before symptoms appear. Biomarkers may also eventually offer better methods to monitor response to treatment.

Learning from families with rare Alzheimer-causing genetic changes
Another new approach to testing experimental drugs to be given before symptoms appear focuses on individuals with rare genetic mutations that guarantee they'll eventually develop Alzheimer's disease. All of these currently known mutations affect beta-amyloid processing or production.

One project is the Alzheimer's Prevention Initiative (API), an international public-private consortium established to conduct research in an extended family in Antioquia, Colombia, in South America. At 5,000 members, this family is the world's largest in which a gene for familial (inherited) Alzheimer's has been identified. Familial Alzheimer's disease is also known as autosomal-dominant Alzheimer's disease (ADAD).

API's first clinical studies will test therapies targeting beta-amyloid in family members who are known to carry the Alzheimer's-causing gene but who have not yet experienced symptoms. Delaying or preventing the appearance of Alzheimer's in these family members could offer compelling evidence for the promise of beta-amyloid as a therapeutic target.

Catalyst to progress

Kenneth S. Kosik, MD, recipient of a 1991 Alzheimer's Association Zenith Fellows Award, played a pivotal role in the early 1990s documenting that the Colombian family's symptoms are due to Alzheimer's disease. He also helped raise awareness of the family's existence among the international research community. To identify the specific gene involved, he enlisted the help of Alison M. Goate, PhD, a former member of the Alzheimer's Association Medical and Scientific Advisory Council. Dr. Goate and her team pinpointed a previously unknown mutation in the presenilin-1 gene on chromosome 14 as the Alzheimer's-causing change affecting this family

API collaborators include the Dominantly Inherited Alzheimer Network (DIAN) study, an international initiative funded by the National Institute on Aging (NIA). DIAN will track participants from families in whom an Alzheimer's-causing mutation has been identified. The goal is to detect physical or mental changes that might distinguish those who inherit a mutation from those who do not. One strategy will involve monitoring brain beta-amyloid levels with PET scans and Pittsburgh compound B (PIB), the first proof-of-concept beta-amyloid detection compound. PIB was developed in part with Alzheimer's Association funding.

Participate in a clinical trial

If you are interested in participating in a current clinical trial, use Alzheimer's Association TrialMatch®, a free individualized service that matches volunteers with trials based on certain criteria, such as stage of disease, current treatments and location. A lack of volunteers for Alzheimer's clinical trials is one of the greatest obstacles slowing the progress of potential new treatments.